Role of hydrogen peroxide preconditioning in mesenchymal stem cell-mediated heart regeneration: Molecular insights

Table 1 Hydrogen peroxide preconditioning promote heart regeneration

Cells	Cellular mechanism(s)	Redox sensitive transcription factor(s)	Pathway(s)	Major findings	Ref.
Adipose-derived stem cells (hASCs)	Survival	Nrf2	-	Increased: Antioxidant response; reduced: Inflammation; bioenergetic adaptation; nuclear factor-kappa B modulation	Garrido Pascual[45]
Cardiomyocytes	Survival	Nrf2	-	Increased: Mitochondrial membrane potential; reduced: Oxidative stress, apoptosis in cardiomyocytes	Dreger et al[58]
Cardiomyocytes	Proliferation and survival	Nrf1 and Nrf2	P38 MAPK and phosphatidylinositol 3-kinase/Akt	Increased: Phase II enzymes and Bcl2; reduced: Oxidative stress, apoptosis, and caspase-3; resistance to oxidative stress in ischemia-reperfusion injury	Angeloni et al[44]
Zebrafish cardiomyocytes	Proliferation and survival	P53	-	Increased: Proliferation and redox homeostasis; reduced: Reactive oxygen species levels and scar formation	Ye et al[59]
Human Wharton's jelly-derived MSCs	Proliferation, survival, and migration	Hypoxia-inducible factor-1α	Akt	Increased: Resistance to oxidative stress and cell viability; reduced: Apoptosis	Nouri et al[34]
Human MSCs	Survival	-	-	Increased: Adhesion	O'Leary[43]
Mice myocytes	Survival	Catalase	-	Regulate calcium handling and improve ventricular diastolic dysfunction; preserve sarcoplasmic reticulum calcium ATPase activity	Qin et al[60]
Wharton's Jelly-derived MSCs	Survival, migration, paracrine effect, and differentiation	-	-	Increased: Neovascularization and interleukin-6; reduced: Fibrosis	Zhang et al[48]
HASCs	Proliferation, paracrine effects, and migration	-	-	Increased: Insulin-like growth factor-1, PFKFB4, pyruvate dehydrogenase kinase isoenzyme 1, resistance to oxidative stress, glycolysis; reduced: Oxidative phosphorylation	Castro et al[49]
Human decidua basalis mesenchymal stem/stromal cells	Proliferation, migration, and survival	-	-	Increased: Colony formation, adhesion, migration, wound-healing, tube formation, and oxidative stress resilience	Khatlani et al[41]
Zebrafish heart lines	Migration, and differentiation	-	MAPK and extracellular signal-regulated kinases 1/2	Increased: Duox and NADPH oxidase 2; reduced: Dusp6	Han et al[50]
Cardiac progenitor cells	Paracrine effect, differentiation, survival	-	-	Increased: Angiogenesis, endothelial cell density, survival, and cardiac function post-I/R injury; reduced: Fibrosis, apoptosis	Pendergrass et al[54]
Mouse cardiac myocytes	Survival and paracrine effect	-	AMP-activated protein kinase and Akt	Increased: Myocyte contractility; selective activation of nitric oxide synthase isoforms	Sartoretto et al[61]
Bone marrow-derived MSCs	Differentiation	-	Notch1	Increased: Flt1, vWF, PECAM1, NK2 homeobox 5, αMHC, Notch1, Wnt11, cardiac repair and regeneration	Boopathy et al[42]

Akt: Protein kinase B; HASCs: Human adipose-derived stem cells; MAPK: Mitogen-activated protein kinase; MSCs: Mesenchymal stem cells; Nrf2: Nuclear factor erythroid 2-related factor 2.